Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization.

Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials.

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.

IL-8 correlates with reduced baseline femoral neck bone mineral density in adults with cystic fibrosis: a single center retrospective study.

Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1ß, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1ß and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.

The enteroendocrine-osseous axis in patients with long-term type 1 diabetes mellitus.

INTRODUCTION: The relationship between the gut and skeleton is increasingly recognized as a component of the regulation of carbohydrate metabolism. The aim of our study was to assess the relationship between bone mineral density (BMD), incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), intestinotrophic peptide glucagon-like peptide-2 (GLP-2) and osteocalcin isoforms in patients with long-term type 1 diabetes (T1D) when compared to healthy controls. METHODS: Eighty two patients with long term T1D, treated in the Department of Metabolic Diseases and 53 healthy controls were recruited to the study. Long term disease duration was defined as lasting for more than 10 years. The control group was selected among age- and sex-matched healthy people. Fasting blood samples were collected to measure levels of incretin hormones (GLP-1, GLP-2, GIP), two forms of osteocalcin (uncarboxylated (ucOC), and carboxylated (cOC)), and additional biochemical parameters associated with glucose and bone metabolism (HbA1c, calcium, phosphorus, 25(OH)D3, PTH). RESULTS: Patients with T1D had higher BMI than in controls (p = 0.02). There was no difference in BMD at the lumbar spine and the femoral neck between patients with long-term T1D and healthy ones. Z-score values in both groups were within normal ranges. The level of GIP was significantly higher in T1D patients (p = 0.0002) in comparison to the healthy ones. The levels of GLP-1 and GLP-2 did not differ between T1D patients and controls. In the T1D group, strong, positive associations were found between serum levels of GLP-1 and cOC (r = 0.546, p < 0.001) and between GLP-1 and total OC (r = 0.51, p < 0.001), also after adjusting for BMI (p < 0.001 and p < 0.001, respectively). Significant positive associations were also found between serum levels of GLP-2 and cOC (r = 0.27, p = 0.013) and between GLP-2 and total OC (r = 0.25, p = 0.018), also in a multivariate regression (p = 0.009, p = 0,175, respectively). Moreover, in T1D patients, GLP-1 correlated positively with the femoral neck BMD (g/cm2) (r = 0.265, p = 0.016) and this association was statistically significant after adjusting for BMI (p = 0.011). These correlations were not present in the control group. The only significant correlation observed in the control group was between OC and BMD of the neck (p = 0.049 for neck BMD g/cm2, and p = 0.041 for neck Z-score). CONCLUSIONS: Our data suggests an effect of gut hormones on bone in long-term T1D, which could be associated with OC activity, however we did not find a direct connection with glucose metabolism. GLP-1 could have a possible, protective role on bone mineral density in patients with T1D. The data from our study suggests that gut hormones could be considered as a new link in the skeleton - pancreatic endocrine loop in patients with T1D.

Bone loss in hepatitis B virus-infected patients can be associated with greater osteoclastic activity independently of the retroviral use.

Nucleoside/nucleotide analogs such as tenofovir, have been used as long-term therapy for the treatment of hepatitis B and side effects such as the reduction in bone mineral density have been associated with their use. To determine the relationships between bone, hormonal, biochemical, and mineral parameters in patients with hepatitis B treated with nucleoside/nucleotide antiviral. A cross-sectional study was conducted with 81 adult patients with chronic hepatitis B infection. Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, and FGF-23, body composition was performed by DXA. Participants, both gender, were divided according to the use of antiretrovirals: Group1: 27 inactive virus carriers without medication; Group2: 27 patients using tenofovir; and Group3: 27 patients using lamivudine or entecavir. DXA readings diagnosed osteopenia in the lumbar spine for 7.4% of individuals in Group1, 15% in Group2, and 3.7% in Group3. For all groups, we observed normal values in bone formation markers, osteocalcin levels as well as parathyroid hormone, insulin growth factor 1, and FGF-23. In all groups, we found increased levels of urinary deoxypyridinoline, a bone resorption marker. Increased levels in the bone resorption markers indicated a high resorptive activity of bone tissue. These data suggested high resorption activity of bone tissue in hepatitis B virus-infected patients independent of the use of antiretrovirals.

Reference values for bone metabolism in a Japanese cohort survey randomly sampled from a basic elderly resident registry.

The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD.

Femoral neck strain prediction during level walking using a combined musculoskeletal and finite element model approach.

Recently, coupled musculoskeletal-finite element modelling approaches have emerged as a way to investigate femoral neck loading during various daily activities. Combining personalised gait data with finite element models will not only allow us to study changes in motion/movement, but also their effects on critical internal structures, such as the femur. However, previous studies have been hampered by the small sample size and the lack of fully personalised data in order to construct the coupled model. Therefore, the aim of this study was to build a pipeline for a fully personalised multiscale (body-organ level) model to investigate the strain levels at the femoral neck during a normal gait cycle. Five postmenopausal women were included in this study. The CT and MRI scans of the lower limb, and gait data were collected for all participants. Muscle forces derived from the body level musculoskeletal models were used as boundary constraints on the finite element femur models. Principal strains were estimated at the femoral neck region during a full gait cycle. Considerable variation was found in the predicted peak strain among individuals with mean peak first principal strain of 0.24% ± 0.11% and mean third principal strain of -0.29% ± 0.24%. For four individuals, two overall peaks of the maximum strains were found to occur when both feet were in contact with the floor, while one individual had one peak at the toe-off phase. Both the joint contact forces and the muscular forces were found to substantially influence the loading at the femoral neck. A higher correlation was found between the predicted peak strains and the gluteus medius (R2 ranged between 0.95 and 0.99) than the hip joint contact forces (R2 ranged between 0.63 and 0.96). Therefore, the current findings suggest that personal variations are substantial, and hence it is important to consider multiple subjects before deriving general conclusions for a target population.

Factors Related to Bone Metabolism in Kidney Transplant Recipients.

This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.

Three pleiotropic loci associated with bone mineral density and lean body mass.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10-8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10-8, replication p = 1.03 × 10-4), 16q12.2 (rs1421085, discovery p = 2.04 × 10-9, replication p = 6.47 × 10-14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10-8, replication p = 6.69 × 10-6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women.

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1-L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO (OR = 1.49, 95% CI 1.0-2.1, P = 0.03). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis.

BACKGROUND: Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. METHODS: Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran's Q test and I2 statistics. RESULTS: A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. CONCLUSION: Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.

Globular structure of the hypermineralized tissue in human femoral neck.

Bone becomes more fragile with ageing. Among many structural changes, a thin layer of highly mineralized and brittle tissue covers part of the external surface of the thin femoral neck cortex in older people and has been proposed to increase hip fragility. However, there have been very limited reports on this hypermineralized tissue in the femoral neck, especially on its ultrastructure. Such information is critical to understanding both the mineralization process and its contributions to hip fracture. Here, we use multiple advanced techniques to characterize the ultrastructure of the hypermineralized tissue in the neck across various length scales. Synchrotron radiation micro-CT found larger but less densely distributed cellular lacunae in hypermineralized tissue than in lamellar bone. When examined under FIB-SEM, the hypermineralized tissue was mainly composed of mineral globules with sizes varying from submicron to a few microns. Nano-sized channels were present within the mineral globules and oriented with the surrounding organic matrix. Transmission electron microscopy showed the apatite inside globules were poorly crystalline, while those at the boundaries between the globules had well-defined lattice structure with crystallinity similar to the apatite mineral in lamellar bone. No preferred mineral orientation was observed both inside each globule and at the boundaries. Collectively, we conclude based on these new observations that the hypermineralized tissue is non-lamellar and has less organized mineral, which may contribute to the high brittleness of the tissue.

Bone turnover markers in serum but not in saliva correlate with bone mineral density.

Saliva was proposed as a diagnostic tool for systemic diseases. Here we determined the correlation of bone turnover markers in saliva, bone turnover markers in serum and bone mineral density in postmenopausal osteoporotic and healthy women. Forty postmenopausal osteoporotic and 40 age-matched healthy non-osteoporotic females were recruited for this case-control study. Serum and stimulated saliva levels of osteocalcin, N-terminal propeptide of type I collagen, bone-specific alkaline phosphatase and cross-linked-C-telopeptide of type I collagen were determined. Bone mineral density of the lumbar spine, proximal femur, and total hip were obtained. We show that osteocalcin and cross-linked-C-telopeptide of type I collagen (CTX) reached detectable levels in saliva while N-terminal propeptide of type I collagen and alkaline phosphatase were close or below the detection limit. Serum levels of bone turnover markers were significantly higher than saliva levels. Correlation analysis revealed a strong correlation of serum osteocalcin and, to a lesser extent, also serum CTX values with bone mineral density in lumbar spine, femoral neck, or total hip, respectively. There was, however, no significant correlation of bone mineral density with the respective bone turnover markers in saliva. There was a trend that saliva osteocalcin correlates with femoral neck (p = 0.16) or total hip (p = 0.06). There was also no association between serum and saliva bone turnover markers. This study reveals that saliva cannot replace the withdrawal of serum to evaluate bone metabolism.

Changes in bone mineral density over 10 years in patients with early rheumatoid arthritis.

OBJECTIVES: To investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period. METHODS: Consecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests. RESULTS: At inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was -0.33 (95 % CI -0.57 to -0.08) in men and -0.07 (-0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value -0.35; 95 % CI -0.61 to -0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was -0.05 (-0.29 to 0.19) and for women 0.06 (-0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen. CONCLUSIONS: In this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5 years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited.

Association between Geriatric Nutrition Risk Index and Skeletal Muscle Mass Index with Bone Mineral Density in Post-Menopausal Women Who Have Undergone Total Thyroidectomy.

BACKGROUND: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. METHODS: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. RESULTS: Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. CONCLUSION: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.

Oxytocin and bone quality in the femoral neck of rats in periestropause.

The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 µg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.

Analysis of the tumor necrosis factor superfamily member 11 gene polymorphism with bone mineral density and bone fracture frequency in patients with postmenopausal osteoporosis.

PURPOSE: We aimed to examine the polymorphism of the promoter and exon 5 of the TNFSF11 gene and their impact on bone mineral density (BMD) and the frequency of bone fractures. TNFSF11 encodes the receptor activator of the NF-kB ligand (RANKL), a key regulator of bone metabolism and osteoporosis drug targets. BMD is an essential measure in diagnosing osteoporosis and assessing the risk of fractures. In vivo, RANKL expression research suggests that promoter TNFSF11 variants influence BMD. Moreover, exon 5 polymorphism of a linear epitope sequence for a denosumab could be related to the effectiveness of biological therapy. PATIENTS AND METHODS: The study included 114 postmenopausal osteoporosis patients. BMD was measured in the lumbar spine and the femoral neck. Genetic analysis was performed using Sanger sequencing. Genotypes data for 263 female European population group were obtained from the 1000Genomes database. RESULTS: We identified six promoter polymorphisms (rs9525641, rs9533155, rs9533156, rs11839112, rs28926171, rs183599708) and one silent TNFSF11 variant in exon 5 (rs9562415). Three of the sequence variants detected (rs9525641, rs9533155, rs9533156) proved to be polymorphic, whereas the others four occurred at a frequency below 2%. The statistical analysis demonstrated no significant differences between polymorphisms and BMD, and bone fractures. However, variant rs9533156 was relevant with the lumbar spine T-score (p = 0.0273), and no association with BMD was of borderline significance (p = 0.0529). CONCLUSIONS: Variant rs9533156 may contribute to the genetic regulation of BMD in Polish postmenopausal osteoporosis, while the exon 5 sequence of the TNFSF11 gene is very conservative.

SEM BSE 3D Image Analysis of Human Incus Bone Affected by Cholesteatoma Ascribes to Osteoclasts the Bone Erosion and VpSEM dEDX Analysis Reveals New Bone Formation.

Bone erosion is considered a typical characteristic of advanced or complicated cholesteatoma (CHO), although it is still a matter of debate if bone erosion is due to osteoclast action, being the specific literature controversial. The purpose of this study was to apply a novel scanning characterization approach, the BSE 3D image analysis, to study the pathological erosion on the surface of human incus bone involved by CHO, in order to definitely assess the eventual osteoclastic resorptive action. To do this, a comparison of BSE 3D image of resorption lacunae (resorption pits) from osteoporotic human femur neck (indubitably of osteoclastic origin) with that of the incus was performed. Surface parameters (area, mean depth, and volume) were calculated by the software Hitachi MountainsMap© from BSE 3D-reconstructed images; results were then statistically analyzed by SPSS statistical software. Our findings showed that no significant differences exist between the two groups. This quantitative approach implements the morphological characterization, allowing us to state that surface erosion of the incus is due to osteoclast action. Moreover, our observation and processing image workflow are the first in the literature showing the presence not only of bone erosion but also of matrix vesicles releasing their content on collagen bundles and self-immuring osteocytes, all markers of new bone formation on incus bone surface. On the basis of recent literature, it has been hypothesized that inflammatory environment induced by CHO may trigger the osteoclast activity, eliciting bone erosion. The observed new bone formation probably takes place at a slower rate in respect to the normal bone turnover, and the process is uncoupled (as recently demonstrated for several inflammatory diseases that promote bone loss) thus resulting in an overall bone loss. Novel scanning characterization approaches used in this study allowed for the first time the 3D imaging of incus bone erosion and its quantitative measurement, opening a new era of quantitative SEM morphology.

Bone Metabolism Parameters in Hemodialysis Patients With Chronic Kidney Disease and in Patients After Kidney Transplantation.

Chronic kidney disease adversely affects the structure and metabolism of bone tissue, which may be a result of disturbed biochemical processes in adipose tissue. Renal replacement therapy is a life-saving therapy but it does not restore all metabolic functions and sometimes even escalates some disturbances. The study included 126 subjects: 47 hemodialysis patients (HD), 56 patients after renal transplantation (Tx) and 23 healthy controls (K). Bone density at the femoral neck (FN) and lumbar spine (LS), as well as body composition (adipose tissue content and lean body mass) were measured in each patient using the DXA method. In addition, serum concentrations of glucose, calcium, phosphorus, parathormone, FGF23, Klotho, osteocalcin, leptin, adiponectin and 1,25-dihydroxyvitamin D3 were measured. We observed significantly higher concentrations of leptin, FGF23 and Klotho proteins in the HD patients (77.2±48.1 ng/ml, 54.7±12.4 pg/ml, 420.6±303.8 ng/ml, respectively) and the Tx group (33.2±26.5 ng/ml; 179.8±383.9 pg/ml; 585.4±565.7, respectively) compared to the control group (24.4±24.6 ng/ml, 43.3±37.3 pg/ml, 280.5±376.0 ng/ml). Significantly lower bone density at FN was observed in the HD and Tx patients in comparison to the controls and in the HD patients compared to the Tx group. There were no significant differences in body mass composition between the studied groups. The results of this study indicate that both hemodialysis and transplantation are associated with increased serum concentrations of leptin, FGF23 and Klotho proteins, as well as lower bone density at femoral neck.